Many investigations have been made in the art for a fairly long time with the intention of producing new cephalosporin compounds having a high antibacterial activity and a high absorption capacity through digestive tracts upon oral administration in combination. Among these compounds, such cephalosporins which are of the type of a 3-substituted thio-3-cephem compound have been considered to be particularly attractive as antibacterial compounds in view of their high absorption capacity through digestive tracts upon oral administration, i.e. excellent absorption in vivo upon oral administration. These 3-substituted thio-3-cephem compounds have been synthesized in the prior art mainly by such method as described in the "Helvetica Chimica Acta", 58, 2437 (1975), wherein the sulfonate or phosphate ester at the 3-enolic hydroxyl group of a 3-hydroxy-3-cephem compound is reacted with a thiol compound in the presence of a base.
However, in the prior art method above-mentioned, the reaction rate of the substitution reaction taking place at the 3-position of the starting cephem compound is not sufficiently high. Thus, in most cases, it was necessary to use the reactant, a thiol compound, and/or a base in excess amount, and occasionally to elevate the reaction temperature in order to proceed with the intended reaction smoothly. The use of such reaction conditions or operations as mentioned above can, sometimes or often, lead to the occurrence of degradation reaction(s) and/or the formation of undesirable secondary product(s), depending upon the natures of side chain at the 7-position and the ester-forming group at the 4-position of the starting cephem compound used. This was one of the major causes for the lowered yield of the 3-substituted thio-3cephem compound formed as the desired final product. In particular, the prior art method usually had a tendency to form the .DELTA..sup.2 isomer, namely such 2-cephem compound in which the transfer of the double bond in the cephem ring occurred during the reaction, and therefore the .DELTA..sup.2 isomer, if formed, had to be isomerized into the desired .DELTA..sup.3 isomer, i.e. the intended 3-cephem compound, by adopting an extra step for achieving such isomerization. A further disadvantage involved in the prior art method above is that some thiol compounds useful as the reactant therein have no good, reasonable method for their synthesis, so that the said prior art method is limited in the range of its application.